1. Field of the Invention
The invention refers to the process for the preparation of 3,14.beta.-dihydroxy-17-normorphinan of this general formula (I): ##STR2## R.dbd.hydrogen.
This compound is a key intermediate within the synthesis of 3,14.beta.-dihydroxy-17-cycloalkylmethylmorphinans of a general formula (II): ##STR3## wherein R.sub.1 .dbd.cyclopropyl or cyclobutyl, which are very effective analgesics, at which no habituation and antagonistic morphine effects are assumed.
2. Description of the Prior Art
Compounds of a general formula (II) were prepared by means of a total synthesis (U.S. Pat. No. 3,819,635), or by means of a semisynthesis from a natural alkaloid thebaine (Mouralova, J. - Hajicek, J. - Trojanek, J.: Ceskoslov. Farm. 1 32, 23 (1983)).
4-phenoxy-14.beta.-hydroxy-3-methoxymorphinan (III) is one of the intermediates of a semisynthesis: ##STR4## wherein R.sub.2 .dbd.CH.sub.3, which is procurable after several synthesis steps from thebaine in a very good yield. Within the following step, a phenoxy-group is removed by means of a reduction with sodium in liquid ammonia, and an intermediate - 14.beta.-hydroxy-3-methoxymorphinan (IV) ##STR5## will be subjected to alkaline hydrolysis after the reaction with phenylchloroformate.
A key intermediate (-)-14.beta.-hydroxy-3-methoxy-17-normorphinan (I) is reached on the basis of all the above-mentioned reactions, in which R.dbd.CH.sub.3. Thus, the demanded compound (II) can be gained by means of several well-known procedures, i.e. either by means of a direct alkylation with cycloalkylmethylhalide, or by means of the O-demethylation (Czech patent appl. PV 163-93), or by means of acylation with cycloalkylcarbonylhalide followed by the reduction of carbonyl with complex hydrides and following O-demethylation (U.S. Pat. No. 3,819,635, Czech patent appl. PV 163-93). The O-demethylation can be ranked before alkylation or acylation, or among acylation and reduction of a carbonyl function.